Differences between Tylenol, Aleve, Advil and Aspirin


Most people have one or more OTC pain relievers at home, but do you know which ones are best for certain types of pain? Or are you just looking for what is comfortable? In general, most people tend to stick with a brand that they recognize or consider "better" than others.

You may wonder if there really are differences between the two. The fact is that they all differ significantly from each other. When you buy them, take them, and especially combine them with each other or with other medications, there are some important facts to know.

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Properties of over-the-counter pain relievers

There are four main OTC pain relievers on the market:

Each has benefits and risks. Although their general function is more or less the same (pain relief), their mechanism of action and the best way to use them differ. Reasons for using them may include some or all of the following:

The choice of drug will largely depend on the condition to be treated and the potential problems that could prevent you from using a particular product.

Cox enzymes and inflammation.

All of these over-the-counter pain relievers affect proteins called COX enzymes , but one of these drugs works differently from the others.

Anti-inflammatory drugs

Ibuprofen, naproxen sodium, and aspirin are non-steroidal anti-inflammatory drugs (NSAIDs) with a similar mechanism of action. Because of this, you should not combine more than one type of NSAID, as this can increase the possibility of side effects. Serious risks associated with taking NSAIDs other than aspirin include an increased risk of heart attack or stroke.

NSAIDs work by blocking COX-1 and COX-2 enzymes outside the central nervous system (CNS) and at the site of tissue damage. COX enzymes are involved in the inflammatory process, so blocking them reduces inflammation and the pain it can cause.


Meanwhile, the mechanism of action of acetaminophen is not fully understood, but it does appear to increase your body's pain threshold (the point at which the sensation is perceived as painful). This is believed to be accomplished by targeting a protein sometimes called COX-3, which is actually a variant of COX-1.

However, the key difference is that acetaminophen blocks this protein within the CNS (brain and spinal cord), rather than outside of it like NSAIDs. This important difference means that acetaminophen is not effective for problems related to inflammation, such as sprains or rheumatoid arthritis .


Acetaminophen is one of the most widely used medications in the United States and is found in several hundred over-the-counter medications, as well as numerous prescription medications. Over-the-counter brands of acetaminophen-containing products include:

  • Tylenol
  • Actamine
  • Febaline
  • Panadol
  • Tempra Quicklets
  • Dyquil (in combination with dextromethorphan and pseudoephedrine )
  • NyQuil Cold / Flu Relief (in combination with dextromethorphan and doxylamine )

You will also find acetaminophen in most medications that are said to relieve sinus pain, such as multi-symptom cold and flu products.

Acetaminophen is also used in a combination of opioid pain relievers, such as:

Best to match

Acetaminophen is widely used because it is not only effective, but it also has fewer side effects than other over-the-counter pain relievers and does not negatively interact with most common medications. This is why it is found in many combination products. Also, because it has a different mechanism of action, acetaminophen can be safely combined with NSAIDs.

Some studies say it is as good as NSAIDs for headaches, while others say it is less effective. However, research has shown that medications that combine acetaminophen, aspirin, and caffeine are better for treating certain types of migraines . This largely depends on the type of headache and your individual response to medications.

However, because acetaminophen does not reduce inflammation, it may be less effective for inflammatory causes of pain, such as arthritis or certain injuries.

Safety measures

Acetaminophen is often combined with opioid pain relievers to treat severe postoperative pain, trauma, or chronic pain. It is generally safe at the recommended dosage, although some people may develop a severe skin rash.

Acetaminophen overdose can cause serious, sometimes fatal, liver damage. It is important to adhere to the recommended dosage. Since acetaminophen is found in many foods, be sure to check the labels of all the medications you take. It also helps involve your PCP and pharmacist in treatment decisions.

However, unlike NSAIDs, acetaminophen is not associated with an increased risk of heart attack or stroke. The American Heart Association recommends acetaminophen as the first pain reliever to try in people who have had a heart attack.

Acetaminophen warnings

Acetaminophen liver toxicity is a major concern in the United States due to the epidemic of opioid abuse and overdose. Many overdose deaths are caused by acetaminophen, not the opioid. Liver damage is also more likely if acetaminophen is combined with alcohol.


Aspirin, also known as acetylsalicylic acid (ASA) , is an NSAID used to treat pain, fever, and inflammation. It is found in many foods, both alone and in combination with other medications. Trademarks include:

  • Regimen to take anacin and aspirin.
  • Bayer
  • Buferin
  • Empirin
  • Genacote
  • Miniprin
  • Uni Buff

Some combination products that contain aspirin:

  • Alka-Seltzer (with citric acid and baking soda )
  • Anacin Advanced Headache Formula (with Acetaminophen and Caffeine)
  • Excedrin (with acetaminophen and caffeine)

It is also found in some prescription combination opioids, including:

  • Combining catfish with codeine
  • Alor, Lortab ASA, Honeycomb (with hydrocodone )
  • Endodan, Percodan, Roxiprin (with oxycodone )

Best for heart health

You've probably heard of taking low-dose aspirin every day for heart health, especially if you've had a heart attack or currently have heart disease. This is beneficial because it prevents the blood from clotting. In people with narrow arteries, a blood clot can block blood flow to the heart or brain and lead to a heart attack or stroke.

However, aspirin is not safe for everyone, and as with any medication, you and your healthcare provider should weigh the potential benefits and risks before deciding whether and what dose a daily aspirin regimen is right for you. the right one.

Safety measures

Excessive bleeding and indigestion are common side effects of aspirin. Stomach ulcers and gastrointestinal bleeding can occur. This occurs more often in people who:

  • Over 70 years
  • Drink alcohol
  • Take other NSAIDs
  • Take blood thinners

If taken during a heart attack, aspirin can significantly reduce the chance of death. On the other hand, it should not be taken for a stroke, as a stroke can be caused by a ruptured vein (rather than a blockage). Therefore, aspirin can make a stroke worse by contributing to bleeding.

Aspirin warnings

Aspirin should be avoided in children with fever due to the risk of Reye's syndrome , which is a form of encephalopathy (brain disease).


Ibuprofen is an NSAID used to treat pain, fever, and inflammation, and is commonly used to relieve symptoms of migraines, menstrual cramps, or rheumatoid arthritis. Like all NSAIDs, ibuprofen is better than acetaminophen for inflammation or disease. Trademarks include:

Combination opioid products that contain ibuprofen include:

  • Ibudon, Replexain, Vicoprofen (with hydrocodone)
  • Combunox (with oxycodone)

Best for fast action

Ibuprofen is a short-acting NSAID that works faster than naproxen. It may be better for acute pain, such as a new injury. The downside is that ibuprofen must be taken more often than naproxen.

Safety measures

Ibuprofen has fewer side effects than some NSAIDs, but it can cause heartburn and rashes. People with kidney or liver problems should avoid it, and if taken in excess, it can increase the risk of hypertension (high blood pressure) and heart attack.

Ibuprofen warnings

Ibuprofen (and all NSAIDs except aspirin) can increase the risk of heart attack or stroke, which can occur suddenly and be fatal. Ibuprofen can also cause serious damage to the stomach or intestines, such as bleeding, sores, or holes.

Naproxen sodium

Naproxen sodium is an NSAID used to treat the same symptoms and conditions as ibuprofen (pain, fever, inflammation, migraine, menstrual cramps, rheumatoid arthritis). It is also sometimes used for chronic painful conditions such as Paget's disease and Bartter's syndrome .

Again, like NSAIDs, naproxen is a better option than acetaminophen for pain associated with inflammation. Trademarks include:

  • Aleve
  • Anaprex
  • Naprosine
  • Aleve PM (with diphenhydramine)

Prescription drugs that contain naproxen include:

Better for chronic pain, fewer side effects

Naproxen is a long-acting NSAID, which means that it takes longer to relieve pain, but lasts longer than a short-acting NSAID like ibuprofen. You also don't need to take it as often. This may make it a better option if you need to take it regularly for pain caused by a chronic condition.

Another real benefit is that naproxen sodium is associated with fewer side effects than ibuprofen, which means it is safer overall and you can tolerate it if ibuprofen bothers you.

Safety measures

Compared to ibuprofen, naproxen has a much higher risk of developing stomach ulcers. Therefore, it should be taken with meals or avoided if you have a history of ulcers or inflammatory bowel disease (IBD) .

Naproxen sodium warnings

Like most NSAIDs, naproxen can increase your risk of heart attack or stroke.

Frequently asked questions

What OTC pain relievers work best on the kidneys?

Acetaminophen is the over-the-counter pain reliever of choice for people with kidney disease because ibuprofen and naproxen can decrease kidney function, and aspirin is associated with bleeding. Still, if you have kidney failure, use acetaminophen in moderation and under the supervision and supervision of your healthcare professional.

What OTC pain relievers are safe to take together?

You should not take more than one drug in a class at a time because it increases the risk of side effects or overdose. This means that it is not safe to combine NSAIDs such as aspirin, ibuprofen, naproxen, or prescription NSAIDs. Because acetaminophen has a different mechanism of action, it can be safely taken with NSAIDs.

Paracetamol Aspirin Ibuprofen Naproxen
Source: ASHP SafeMedication

What OTC pain relievers are not NSAIDs?

Acetaminophen is the only OTC pain reliever that is not an NSAID. Many over-the-counter pain relievers do not contain NSAIDs.

Are Over-the-Counter Pain Relievers Safe During Pregnancy?

Acetaminophen is considered the safest OTC pain reliever to take during pregnancy, but only for short-term use. Birth defects were less common with acetaminophen during pregnancy than with NSAIDs or opioids, according to a study by the Centers for Disease Control and Prevention.

As with anything you take during pregnancy, be sure to speak with your midwife before use.

What OTC pain relievers can I take with blood thinners?

Acetaminophen is a recommended over-the-counter pain reliever for people taking blood thinners , but it should even only be taken with the knowledge and supervision of your healthcare provider. NSAIDs, and especially aspirin, can prevent blood from clotting, so combining them with blood-thinning medications such as Coumadin (warfarin) can increase the risk of serious or even fatal bleeding.

Get the word of drug information

When choosing the right pain reliever, it is important to consider side effects and possible drug interactions. Talk to your doctor about which one might be best for you.

If you are in a pharmacy and need last minute advice, especially if you have a medical condition or are taking any medications, you can also ask your pharmacist.

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